The role for which she is best known is Abigaille in Verdi's opera Nabucco. She made a recording of this role for Decca/London in 1965 (opposite Tito Gobbi, and conducted by Lamberto Gardelli), and gave a performance of the role on opening night of La Scala's 1966-67 season. Within the next couple of years, she also recorded Santuzza (with Mario del Monaco and Gobbi, 1966) and the title role in Norma (with del Monaco, 1967), the latter in an abridged recording that was much maligned when it was initially released.

She made her London debut on 3 November 1968, when she sang Abigaille in a concert performance of Nabucco at the Theatre Royal, Drury Lane, an event mounted by the London Opera Society. The cast also included Piero Cappuccilli and Boris Christoff, and the conductor was Mario Gusella. In June 1969, she made her debut at the Royal Opera House, Covent Garden, singing Lady Macbeth for the first time.

Souliotis was scheduled to make her Metropolitan Opera debut as Lady Macbeth during the 1969-70 season. However, due to a strike, the first few months of the season were canceled. Souliotis never sang at the Met.

The received opinion is that Souliotis's early assumption of difficult roles damaged her voice. After an absence from the stage that lasted several years, she began a second career in secondary roles, beginning in 1979. She sang Fata Morgana in Sergei Prokofiev's The Love for Three Oranges in Chicago and Florence, and went on to sing in such operas as Prokofiev's The Gambler and Puccini's Suor Angelica, in the latter as the Zia Principessa. Her recording of this latter role, in 1991, opposite Mirella Freni, was her final studio recording. Toward the end of her career, she sang the role of the Comtesse in Tchaikovsky's The Queen of Spades in several venues, and gave her farewell to the operatic stage in this role in Stuttgart in February 2000.

Elena Souliotis died of heart failure in 2004 in Florence, Italy, aged 61.